HIV DNA reservoir and elevated PD-1 expression of CD4 T-cell subsets particularly persist in the terminal ileum of HIV-positive patients despite cART.

OBJECTIVES: Despite its importance as an HIV anatomic sanctuary, little is known about the characteristics of the HIV reservoir in the terminal ileum (TI). In blood, the immune checkpoint inhibitor programmed-death-1 (PD-1) has been linked to the HIV reservoir and T-cell immune dysfunction. We thus evaluated PD-1 expression and cell-associated HIV DNA in memory CD4 T-cell subsets from TI, peripheral blood (PB) and rectum (RE) of untreated and treated HIV-positive patients to identify associations between PD-1 and HIV reservoir in other sites. METHODS: Using mononuclear cells from PB, TI and RE of untreated HIV-positive (N = 6), treated (n = 18) HIV-positive and uninfected individuals (n = 16), we identified and sorted distinct memory CD4 T-cell subsets by flow cytometry, quantified their cell-associated HIV DNA using quantitative PCR and assessed PD-1 expression levels using geometric mean fluorescence intensity. Combined HIV-1 RNA in situ hybridization and immunohistochemistry was performed on ileal biopsy sections. RESULTS: Combined antiretroviral therapy (cART)-treated patients with undetectable HIV RNA and significantly lower levels of HIV DNA in PB showed particularly high PD-1 expression in PB and TI, and high HIV DNA levels in TI, irrespective of clinical characteristics. By contrast, in treatment-naïve patients HIV DNA levels in memory CD4 T-cell subsets were high in PB and TI. CONCLUSION: Elevated PD-1 expression on memory CD4 T-cells in PB and TI despite treatment points to continuous immune dysfunction and underlines the importance of evaluating immunotherapy in reversing HIV latency and T-cell reconstitution. As HIV DNA particularly persists in TI despite cART, investigating samples from TI is crucial in understanding HIV immunopathogenesis.

Generic Optical Excitations of Correlated Systems: π-tons.

The interaction of light with solids gives rise to new bosonic quasiparticles, with the exciton being-undoubtedly-the most famous of these polaritons. While excitons are the generic polaritons of semiconductors, we show that for strongly correlated systems another polariton is prevalent-originating from the dominant antiferromagnetic or charge density wave fluctuations in these systems. As these are usually associated with a wave vector (π,π,…) or close to it, we propose to call the derived polaritons π-tons. These π-tons yield the leading vertex correction to the optical conductivity in all correlated models studied: the Hubbard, the extended Hubbard model, the Falicov-Kimball, and the Pariser-Parr-Pople model, both in the insulating and in the metallic phase.

Progress in global rollout of new multidrug-resistant tuberculosis treatments.

SETTING: The global multidrug-resistant tuberculosis (MDR-TB) epidemic has grown over the past decade and continues to be difficult to manage. In response, new drugs and treatment regimens have been recommended.OBJECTIVE: In 2017 and again in 2018, the International Union Against Tuberculosis and Lung Disease (The Union) drug-resistant (DR) TB Working Group collaborated with RESIST-TB to implement an internet survey to members of The Union around the world to assess access to these new treatment strategies.DESIGN: A nine-question survey was developed using SurveyMonkey®. The survey was open for participation to all members of The Union registered under the TB Section. Two reminders were sent during each survey. The responses were analyzed taking into account the WHO Region to which the respondent belonged.RESULTS: The 2018 survey showed a global increase in implementation of the shorter (9-month) MDR-TB regimen (from 33% to 56% of respondents, P < 0.001) and an increase in the use of bedaquiline and/or delamanid (from 25% to 41% of respondents, P < 0.001) compared to 2017. There were substantial variations in roll-out between WHO regions.CONCLUSION: These results demonstrate improvement in global implementation of the new treatment strategies over a 1-year period.

Quantum Criticality in the Two-Dimensional Periodic Anderson Model.

We study the phase diagram and quantum critical region of one of the fundamental models for electronic correlations: the periodic Anderson model. Employing the recently developed dynamical vertex approximation, we find a phase transition between a zero-temperature antiferromagnetic insulator and a Kondo insulator. In the quantum critical region, we determine a critical exponent γ=2 for the antiferromagnetic susceptibility. At higher temperatures, we have free spins with γ=1 instead, whereas at lower temperatures, there is an even stronger increase and suppression of the susceptibility below and above the quantum critical point, respectively.

Radiation epidemiology and health effects following low-level radiation exposure.

Radiation epidemiology is the study of human disease following radiation exposure to populations. Epidemiologic studies of radiation-exposed populations have been conducted for nearly 100 years, starting with the radium dial painters in the 1920s and most recently with large-scale studies of radiation workers. As radiation epidemiology has become increasingly sophisticated it is used for setting radiation protection standards as well as to guide the compensation programmes in place for nuclear weapons workers, nuclear weapons test participants, and other occupationally exposed workers in the United States and elsewhere. It is known with high assurance that radiation effects at levels above 100-150 mGy can be detected as evidenced in multiple population studies conducted around the world. The challenge for radiation epidemiology is evaluating the effects at low doses, below about 100 mGy of low-linear energy transfer radiation, and assessing the risks following low dose-rate exposures over years. The weakness of radiation epidemiology in directly studying low dose and low dose-rate exposures is that the signal, i.e. the excess numbers of cancers associated with low-level radiation exposure, is so very small that it cannot be seen against the very high background occurrence of cancer in the population, i.e. a lifetime risk of incidence reaching up to about 38% (i.e. 1 in 3 persons will develop a cancer in their lifetime). Thus, extrapolation models are used for the management of risk at low doses and low dose rates, but having adequate information from low dose and low dose-rate studies would be highly desirable. An overview of recently conducted radiation epidemiologic studies which evaluate risk following low-level radiation exposures is presented. Future improvements in risk assessment for radiation protection may come from increasingly informative epidemiologic studies, combined with mechanistic radiobiologic understanding of adverse outcome pathways, with both incorporated into biologically based models.

TOPAS-nBio: An Extension to the TOPAS Simulation Toolkit for Cellular and Sub-cellular Radiobiology.

The TOPAS Monte Carlo (MC) system is used in radiation therapy and medical imaging research, having played a significant role in making Monte Carlo simulations widely available for proton therapy related research. While TOPAS provides detailed simulations of patient scale properties, the fundamental unit of the biological response to radiation is a cell. Thus, our goal was to develop TOPAS-nBio, an extension of TOPAS dedicated to advance understanding of radiobiological effects at the (sub-)cellular, (i.e., the cellular and sub-cellular) scale. TOPAS-nBio was designed as a set of open source classes that extends TOPAS to model radiobiological experiments. TOPAS-nBio is based on and extends Geant4-DNA, which extends the Geant4 toolkit, the basis of TOPAS, to include very low-energy interactions of particles down to vibrational energies, explicitly simulates every particle interaction (i.e., without using condensed histories) and propagates radiolysis products. To further facilitate the use of TOPAS-nBio, a graphical user interface was developed. TOPAS-nBio offers full track-structure Monte Carlo simulations, integration of chemical reactions within the first millisecond, an extensive catalogue of specialized cell geometries as well as sub-cellular structures such as DNA and mitochondria, and interfaces to mechanistic models of DNA repair kinetics. We compared TOPAS-nBio simulations to measured and published data of energy deposition patterns and chemical reaction rates (G values). Our simulations agreed well within the experimental uncertainties. Additionally, we expanded the chemical reactions and species provided in Geant4-DNA and developed a new method based on independent reaction times (IRT), including a total of 72 reactions classified into 6 types between neutral and charged species. Chemical stage simulations using IRT were a factor of 145 faster than with step-by-step tracking. Finally, we applied the geometric/chemical modeling to obtain initial yields of double-strand breaks (DSBs) in DNA fibers for proton irradiations of 3 and 50 MeV and compared the effect of including chemical reactions on the number and complexity of DSB induction. Over half of the DSBs were found to include chemical reactions with approximately 5% of DSBs caused only by chemical reactions. In conclusion, the TOPAS-nBio extension to the TOPAS MC application offers access to accurate and detailed multiscale simulations, from a macroscopic description of the radiation field to microscopic description of biological outcome for selected cells. TOPAS-nBio offers detailed physics and chemistry simulations of radiobiological experiments on cells simulating the initially induced damage and links to models of DNA repair kinetics.

A New Standard DNA Damage (SDD) Data Format.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

Local magnetic moments in iron and nickel at ambient and Earth's core conditions.

Some Bravais lattices have a particular geometry that can slow down the motion of Bloch electrons by pre-localization due to the band-structure properties. Another known source of electronic localization in solids is the Coulomb repulsion in partially filled d or f orbitals, which leads to the formation of local magnetic moments. The combination of these two effects is usually considered of little relevance to strongly correlated materials. Here we show that it represents, instead, the underlying physical mechanism in two of the most important ferromagnets: nickel and iron. In nickel, the van Hove singularity has an unexpected impact on the magnetism. As a result, the electron-electron scattering rate is linear in temperature, in violation of the conventional Landau theory of metals. This is true even at Earth's core pressures, at which iron is instead a good Fermi liquid. The importance of nickel in models of geomagnetism may have therefore to be reconsidered.

Interplay of Correlations and Kohn Anomalies in Three Dimensions: Quantum Criticality with a Twist.

A general understanding of quantum phase transitions in strongly correlated materials is still lacking. By exploiting a cutting-edge quantum many-body approach, the dynamical vertex approximation, we make important progress, determining the quantum critical properties of the antiferromagnetic transition in the fundamental model for correlated electrons, the Hubbard model in three dimensions. In particular, we demonstrate that-in contradiction to the conventional Hertz-Millis-Moriya theory-its quantum critical behavior is driven by the Kohn anomalies of the Fermi surface, even when electronic correlations become strong.

Multiple irradiation sensing of the optical effective attenuation coefficient for spectral correction in handheld OA imaging.

Spectral optoacoustic (OA) imaging enables spatially-resolved measurement of blood oxygenation levels, based on the distinct optical absorption spectra of oxygenated and de-oxygenated blood. Wavelength-dependent optical attenuation in the bulk tissue, however, distorts the acquired OA spectrum and thus makes quantitative oxygenation measurements challenging. We demonstrate a correction for this spectral distortion without requiring a priori knowledge of the tissue optical properties, using the concept of multiple irradiation sensing: recording the OA signal amplitude of an absorbing structure (e.g. blood vessel), which serves as an intrinsic fluence detector, as function of irradiation position. This permits the reconstruction of the bulk effective optical attenuation coefficient µeff,λ . If performed at various irradiation wavelengths, a correction for the wavelength-dependent fluence attenuation is achieved, revealing accurate spectral information on the absorbing structures. Phantom studies were performed to show the potential of this technique for handheld clinical combined OA and ultrasound imaging.

Magnetic Behavior of Volborthite Cu_{3}V_{2}O_{7}(OH)_{2}·2H_{2}O Determined by Coupled Trimers Rather than Frustrated Chains.

Motivated by recent experiments on volborthite single crystals showing a wide 1/3-magnetization plateau, we perform microscopic modeling by means of density functional theory (DFT) with the single-crystal structural data as a starting point. Using DFT+U, we find four leading magnetic exchanges: antiferromagnetic J and J_{2}, as well as ferromagnetic J^{'} and J_{1}. Simulations of the derived spin Hamiltonian show good agreement with the experimental low-field magnetic susceptibility and high-field magnetization data. The 1/3-plateau phase pertains to polarized magnetic trimers formed by strong J bonds. An effective J→∞ model shows a tendency towards condensation of magnon bound states preceding the plateau phase.

Ultrafast and Gigantic Spin Injection in Semiconductors.

The injection of spin currents in semiconductors is one of the big challenges of spintronics. Motivated by the ultrafast demagnetization and spin injection into metals, we propose an alternative femtosecond route based on the laser excitation of superdiffusive spin currents in a ferromagnet such as Ni. Our calculations show that even though only a fraction of the current crosses the Ni-Si interface, the laser-induced creation of strong transient electrical fields at a ferromagnet-semiconductor interface allows for the injection of chargeless spin currents with record spin polarizations of 80%. Beyond that they are pulsed on the time scale of 100 fs which opens the door for new experiments and ultrafast spintronics.

Controlled lateral anisotropy in correlated manganite heterostructures by interface-engineered oxygen octahedral coupling.

Controlled in-plane rotation of the magnetic easy axis in manganite heterostructures by tailoring the interface oxygen network could allow the development of correlated oxide-based magnetic tunnelling junctions with non-collinear magnetization, with possible practical applications as miniaturized high-switching-speed magnetic random access memory (MRAM) devices. Here, we demonstrate how to manipulate magnetic and electronic anisotropic properties in manganite heterostructures by engineering the oxygen network on the unit-cell level. The strong oxygen octahedral coupling is found to transfer the octahedral rotation, present in the NdGaO3 (NGO) substrate, to the La2/3Sr1/3MnO3 (LSMO) film in the interface region. This causes an unexpected realignment of the magnetic easy axis along the short axis of the LSMO unit cell as well as the presence of a giant anisotropic transport in these ultrathin LSMO films. As a result we possess control of the lateral magnetic and electronic anisotropies by atomic-scale design of the oxygen octahedral rotation.

Surface Effects on the Mott-Hubbard Transition in Archetypal V{2}O{3}.

We present an experimental and theoretical study exploring surface effects on the evolution of the metal-insulator transition in the model Mott-Hubbard compound Cr-doped V{2}O{3}. We find a microscopic domain formation that is clearly affected by the surface crystallographic orientation. Using scanning photoelectron microscopy and x-ray diffraction, we find that surface defects act as nucleation centers for the formation of domains at the temperature-induced isostructural transition and favor the formation of microscopic metallic regions. A density-functional theory plus dynamical mean-field theory study of different surface terminations shows that the surface reconstruction with excess vanadyl cations leads to doped, and hence more metallic, surface states, which explains our experimental observations.

Unified Picture for the Colossal Thermopower Compound FeSb2.

We identify the driving mechanism of the gigantic Seebeck coefficient in FeSb2 as the phonon-drag effect associated with an in-gap density of states that we demonstrate to derive from excess iron. We accurately model electronic and thermoelectric transport coefficients and explain the so far ill-understood correlation of maxima and inflection points in different response functions. Our scenario has far-reaching consequences for attempts to harvest the spectacular power factor of FeSb2.

Momentum-resolved spin dynamics of bulk and surface excited States in the topological insulator Bi(2)Se(3).

The prospect of optically inducing and controlling a spin-polarized current in spintronic devices has generated wide interest in the out-of-equilibrium electronic and spin structure of topological insulators. In this Letter we show that only measuring the spin intensity signal over several orders of magnitude by spin-, time-, and angle-resolved photoemission spectroscopy can provide a comprehensive description of the optically excited electronic states in Bi_{2}Se_{3}. Our experiments reveal the existence of a surface resonance state in the second bulk band gap that is benchmarked by fully relativistic ab initio spin-resolved photoemission calculations. We propose that the newly reported state plays a major role in the ultrafast dynamics of the system, acting as a bottleneck for the interaction between the topologically protected surface state and the bulk conduction band. In fact, the spin-polarization dynamics in momentum space show that these states display macroscopically different temperatures and, more importantly, different cooling rates over several picoseconds.

Electronic reconstruction at the isopolar LaTiO(3)/LaFeO(3) interface: an X-ray photoemission and density-functional theory study.

We report the formation of a nonmagnetic band insulator at the isopolar interface between the antiferromagnetic Mott-Hubbard insulator LaTiO_{3} and the antiferromagnetic charge transfer insulator LaFeO_{3}. By density-functional theory calculations, we find that the formation of this interface state is driven by the combination of O band alignment and crystal field splitting energy of the t_{2g} and e_{g} bands. As a result of these two driving forces, the Fe 3d bands rearrange and electrons are transferred from Ti to Fe. This picture is supported by x-ray photoelectron spectroscopy, which confirms the rearrangement of the Fe 3d bands and reveals an unprecedented charge transfer up to 1.2±0.2 e^{-}/interface unit cell in our LaTiO_{3}/LaFeO_{3} heterostructures.

From infinite to two dimensions through the functional renormalization group.

We present a novel scheme for an unbiased, nonperturbative treatment of strongly correlated fermions. The proposed approach combines two of the most successful many-body methods, the dynamical mean field theory and the functional renormalization group. Physically, this allows for a systematic inclusion of nonlocal correlations via the functional renormalization group flow equations, after the local correlations are taken into account nonperturbatively by the dynamical mean field theory. To demonstrate the feasibility of the approach, we present numerical results for the two-dimensional Hubbard model at half filling.

Poor man's understanding of kinks originating from strong electronic correlations.

By means of dynamical mean field theory calculations, it was recently discovered that kinks generically arise in strongly correlated systems, even in the absence of external bosonic degrees of freedoms such as phonons. However, the physical mechanism behind these kinks remained unclear. On the basis of the perturbative and numerical renormalization group theory, we herewith identify these kinks as the effective Kondo energy scale of the interacting lattice system which is shown to be smaller than the width of the central peak.